Alzheimer's disease (AD) is an emerging public health crisis that poses a huge societal burden. The total payments in 2015 for all individuals with AD are estimated at $226 billion in US. To reduce the cost of AD care, inexpensive preliminary imaging screening with a primary-care setting is one of the keys. However, currently available imaging diagnostic technologies, such as expensive PET imaging, are nearly prohibitive for this need. Near infrared fluorescence (NIRF) imaging is an ideal choice for low cost. Nonetheless, no prior studies have shown the translational feasibility of NIRF imaging for clinical AD research, due to the limitation of tissue penetration of NIRF imaging. In this application, considering retina as a window to a brain, we propose to validate the feasibility of NIRF Ocular Imaging (NIRFOI) for translational AD studies. With NIRFOI, preliminary imaging screening of AD with a primary-care setting could be possible. For NIRF imaging, eye is a very ideal organ, due to its minimal opacity. Anatomically and developmentally, retina is known as an extension of the CNS, and retina is widely considered as a window to the brain. Therefore, retina can be considered as an alternative organ for investigating neurodegenerative diseases. Numerous references have provided strong evidence that ocular pathology can be predictive for CNS diseases. In particular, amyloid beta (A?) deposits in retina has been approved to be highly associated with the loading of A? in brains. Our previous studies demonstrated that NIRF imaging probes CRANAD-X (X = -2, -3, - 30, -58, and -102) were ?smart? fluorescent probes for soluble and insoluble A? species, and could be used to non-invasively image A?s in brains of AD mice. Remarkably, our preliminary data suggested that NIRFOI with CRANAD-X could be used to report ocular A? loadings in the eyes of transgenic AD mice. In this proposal, we will first further screen CRANAD-X library with NIFOI in transgenic AD mice to seek the best candidates, and then natural ageing beagle dogs with and without dementia syndromes will be used to investigate the feasibility of NIRFOI for large animal models. Lastly, we will investigate the practicability of NIRFOI in non-human primates. If NIRFOI is validated in this proposal in all of the species, we will be ready to apply for clinical trials. For a long term, we believe that NIRFOI can be a potential imaging technology for fast, cheap, widely applicable and preliminarily diagnostic screen of a large population with a primary-care setting in the future, and the ?positive? screening results of NIRFOI could be further confirmed with expensive PET imaging and other diagnostic methods. Therefore, NIRFOI can be used as an important complementary tool for AD diagnosis, and have the potential to significantly reduce the care cost of AD.